The innate immune response to virus infection has a strong influence on virus infection in the brain and the clinical outcome of disease. Our studies have focused on animal models of virus-mediated neuropathogenesis to determine the host response proteins that regulate disease induction for virus replication and viral pathogenesis. In 2018, we developed a model for vertical transmission (VTn) of Zika virus to fetuses (Winkler et al. Immunology 2018). This model was based on our previously published work on Zika virus (Winkler et al. J. Immunol. 2017, Winkler et al. Sci. Rep. 2017). This model is currently being used to analyze how virus is transmitted from the dam to the fetus, the role of innate immune cells in this viral transmission, how the virus is transmitted to the brain in the fetus and the role of the innate immune response to brain damage in the fetus. We also examined the pathogenesis of different California Serogroup of Orthobunyaviruses (CSG viruses). We analyzed 5 CSG viruses that cause varying degrees of encephalitis in humans by developing mouse models of virus infections. We found strong correlations between neurological disease incidence in humans and the ability to induce disease in mice (Evans et al. Emerging Inf. Disease 2019). Current research is focused on examining how these viruses differ in their ability to induce disease and what viral/host factors are responsible for this difference.